Oligodendrocytes (from
Greek 'cells with a few branches'), also known as oligodendroglia, are a type of
neuroglia whose main functions are to provide support and insulation to
axons within the
central nervous system (CNS) of
jawed vertebrates. Their function is similar to that of
Schwann cells, which perform the same task in the
peripheral nervous system (PNS). Oligodendrocytes accomplish this by forming the
myelin sheath around axons.[1] Unlike Schwann cells, a single oligodendrocyte can extend its processes to cover around 50 axons,[2] with each axon being wrapped in approximately 1 μm of myelin sheath. Furthermore, an oligodendrocyte can provide myelin segments for multiple adjacent axons.[1]
Oligodendrocytes are exclusively found in the CNS, which comprises the
brain and
spinal cord. Initially, it was originally thought that these cells were produced in the ventral
neural tube, the
embryonic precursor to the CNS. However, recent research suggests that oligodendrocytes originate from the ventral
ventricular zone of the embryonic spinal cord, with some potential concentrations in the
forebrain.[3] Notably, oligodendrocytes are the last type of cell to be generated in the CNS.[4] Oligodendrocytes were discovered by
Pío del Río Hortega.[5][6]
Most oligodendrocytes develop during
embryogenesis and early postnatal life from restricted periventricular germinal regions.[11] Oligodendrocyte formation in the adult brain is associated with glial-restricted
progenitor cells, known as
oligodendrocyte progenitor cells (OPCs).[12]Subventricular zone cells migrate away from
germinal[12] zones to populate both developing
white and
gray matter, where they differentiate and mature into myelin-forming oligodendrocytes.[13] However, it is not clear whether all oligodendrocyte progenitors undergo this sequence of events.[citation needed]
Between midgestation and term birth in human cerebral white matter, three successive stages of the classic human oligodendrocyte lineage are found: OPCs, immature oligodendrocytes (non-myelinating), and mature oligodendrocytes (myelinating).[14] It has been suggested that some undergo
apoptosis[15] and others fail to differentiate into mature oligodendrocytes but persist as adult OPCs.[16] Remarkably, oligodendrocyte population originated in the subventricular zone can be dramatically expanded by administering
epidermal growth factor (EGF).[17][18]
Mammalian
nervous systems depend crucially on myelin sheaths, which reduce ion leakage and decrease the capacitance of the
cell membrane, for rapid signal conduction.[19] Myelin also increases impulse speed, as
saltatory propagation of
action potentials occurs at the
nodes of Ranvier in between Schwann cells (of the PNS) and oligodendrocytes (of the CNS). Furthermore, impulse speed of myelinated axons increases linearly with the axon diameter, whereas the impulse speed of unmyelinated cells increases only with the square root of the diameter. The insulation must be proportional to the diameter of the fibre inside. The optimal ratio of axon diameter divided by the total fiber diameter (which includes the myelin) is 0.6.[20]
Myelination is only prevalent in a few brain regions at birth and continues into adulthood. The entire process is not complete until about 25–30 years of age.[20] Myelination is an important component of intelligence, and white matter quantity may be positively correlated with IQ test results in children.[20] Rats that were raised in an enriched environment, which is known to increase
cognitive flexibility, had more myelination in their
corpus callosi.[21]
It is hypothesized that satellite oligodendrocytes (or perineuronal oligodendrocytes) are functionally distinct from other oligodendrocytes. They are not attached to neurons via myelin sheaths and, therefore, do not contribute to insulation. They remain opposed to neurons and regulate the
extracellular fluid.[24] Satellite oligodendrocytes are considered to be a part of the grey matter whereas myelinating oligodendrocytes are a part of the white matter. They may support neuronal metabolism. Satellite oligodendrocytes may be recruited to produce new myelin after a demyelinating injury.[25]
Diseases that result in injury to oligodendrocytes include demyelinating diseases such as
multiple sclerosis and various
leukodystrophies. Trauma to the body, e.g. spinal cord injury, can also cause demyelination. The immature oligodendrocytes, which increase in number during mid-
gestation, are more vulnerable to
hypoxic injury and are involved in
periventricular leukomalacia.[26] This largely congenital condition of damage to the newly forming brain can therefore lead to
cerebral palsy. In cerebral palsy, spinal cord injury, stroke and possibly multiple sclerosis, oligodendrocytes are thought to be damaged by excessive release of the
neurotransmitter,
glutamate.[27] Damage has also been shown to be mediated by
N-methyl-D-aspartate receptors.[27] Oligodendrocyte dysfunction may also be implicated in the
pathophysiology of
schizophrenia and
bipolar disorder.[28]
Oligodendrocytes are also susceptible to infection by the
JC virus, which causes
progressive multifocal leukoencephalopathy (PML), a condition that specifically affects white matter, typically in
immunocompromised patients.
Tumors of oligodendrocytes are called
oligodendrogliomas. The chemotherapy agent
Fluorouracil (5-FU) causes damage to the oligodendrocytes in mice, leading to both acute
central nervous system (CNS) damage and progressively worsening delayed degeneration of the CNS.[29][30]
DNA methylation may also have a role in the degeneration of oligodendrocytes.[31]
^
abCarlson, Neil (2010). Physiology of Behavior. Boston, MA: Allyn & Bacon. pp. 38–39.
ISBN978-0-205-66627-0.
^Baumann, Nicole; Pham-Dinh, Danielle (2001-04-01). "Biology of Oligodendrocyte and Myelin in the Mammalian Central Nervous System". Physiological Reviews. 81 (2): 871–927.
doi:
10.1152/physrev.2001.81.2.871.
ISSN0031-9333.
PMID11274346.
^Juraska J. M.; Kopcik J. R. (1988). "Sex and environmental influences on the size and ultrastructure of the rat corpus callosum". Brain Research. 450 (1–2): 1–8.
doi:
10.1016/0006-8993(88)91538-7.
PMID3401704.
S2CID2720782.
Raine, C.S. (1991). Oligodendrocytes and central nervous system myelin. In Textbook of Neuropathology, second edition, R.L. Davis and D.M. Robertson, eds. (Baltimore, Maryland: Williams and Wilkins), pp. 115–141.